tailieunhanh - Báo cáo y học: "Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: " Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability | Theoretical Biology and Medical Modelling BioMed Central Research Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability Shakti Gupta Eric Aslakson Brian M Gurbaxani and Suzanne D Vernon Open Access Address Division of Viral and Rickettsial Diseases National Center for Zoonotic Vector-Borne and Enteric Diseases Centers for Disease Control and Prevention 600 Clifton Rd MS-A15 Atlanta Georgia 30333 USA Email Shakti Gupta - shaktig@ Eric Aslakson - btl0@ Brian M Gurbaxani - buw8@ Suzanne D Vernon - svernon@ Corresponding author Published 14 February 2007 Theoretical Biology and Medical Modelling 2007 4 8 doi l 742-4682-4-8 Received 27 August 2006 Accepted 14 February 2007 This article is available from http content 4 1 8 2007 Gupta et al licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract Background The body s primary stress management system is the hypothalamic pituitary adrenal HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body s cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. Results We developed a structured model of the HPA axis that includes the glucocorticoid receptor GR . This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states low and high and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model low GR concentration represents the normal